connecting the dots

Solve Problems with Knowledge Graphs

by Paula Perez

Goals for representing knowledge

· Make things (articles, genes, antibodies, etc.) easier to find · Answer questions · Generate hypotheses controlled vocabularies (MeSH) ontologies (Gene Ontology) knowledge graphs on the Web: the SPARQL query languageknowledge plus computation = inference, the ABC model

Attachments include information that complements slide content. The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Ontology

The word comes from philosophy:

“the branch of metaphysics dealing with the nature of being”

In practice they are:

A set of concepts, definitions and inter-relationships.

The dividing line between “controlled vocabulary”, “thesaurus”, “ontology” is hazy and not terribly important for practical purposes.

We have hundreds of ontologies in biology.

Attachments include information that complements slide content. The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Gene Ontology

Started in 1999 as a collaboration among three Model Organism Databases

GO:0008150biological_processGO:0022607cellular componentassemblyGO:0016043cellular componentorganizationGO:0009987cellular processGO:0071840cellular componentorganization orbiogenesisGO:0048856anatomical structuredevelopmentGO:0044763single-organism cellularprocessGO:0030198extracellular matrixorganizationGO:0043062extracellular structureorganizationGO:0009888tissue developmentGO:0071470cellular response toosmotic stressGO:0006972hyperosmotic responseGO:0071214cellular response toabiotic stimulusGO:0006970response to osmoticstressGO:0033554cellular response tostressGO:0009628response to abioticstimulusGO:0051716cellular response tostimulusGO:0006950response to stressGO:0050896response to stimulusMore specific conceptLess specific concept

Gene Ontology (GO)

A way to capture biological knowledge for individual gene products in a computable form

A set of concepts and their relationships to each other arranged as a hierarchy

OntologySlide credit: Mélanie Courtot, Ph.D.

https://www.ebi.ac.uk/QuickGO/

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie
· protein kinase activity· insulin receptor activity· mitochondrion· mitochondrial matrix· mitochondrial inner membraneinsulin receptorinsulin

GO Branches

subtitle

Molecular Function

An elemental activity or task or job

Biological Process

A commonly recognized series of events

Cellular Component

Where a gene product is located

OntologySlide credit: Mélanie Courtot, Ph.D.

https://www.ebi.ac.uk/QuickGO/

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie
WISDOMKNOWLEDGEINFORMATIONDATAKnowing what to do with Drug A ...Drug A caused Gene X to be expressedGene X is expressedRNASeq reads

Knowledge Graphs

Also called “knowledge bases” to distinguish them from databases.

An integrated collection of assertions or claims represented in something that can be visualized as a graph and is technically very much like a database.

Example knowledge graphs

Wikidata: The structured equivalent of Wikipedia

UniProt Knowledge Base: Manually curated Protein knowledge base

Microsoft Knowledge Graph (“Satori”)

Google Knowledge Graph

Attachments include information that complements slide content. The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Example: Google Knowledge Graph

search for: Vemurafenib

2,310,000 results

1 infobox

1 node in Google Knowledge Graph

Why Knowledge Graphs?

Answer explicit questions; uncover implicit relations

?

Implicit relations for hypothesis generation

ABC model

Co-occurs in an article withRaynaud’s SyndromeACo-occurs in an article withBC?Dietary fish oil· platelet inhibition· vasodilation· lower blood viscosity

Attachments include information that complements slide content. The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Open Discovery and Closed Discovery

Open, you don’t know what C or B is (e.g. disease -> ?drug)

Closed, you know what C is and are looking for B (e.g. disease – why? – drug)

ABC?
DRUGNameRegistered IndicationNew Indicationrepurposing potentialDISEASEKnown Drug in DrugBankNumber of Medline AbstractsNumber in Clinical Trial RegistryRepurposing Potential

Example question: drug repurposing

For a given drug, what diseases might it be used to treat?

Attachments include information that complements slide content. The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Implicit relations for hypothesis generation

ABC model for drug repurposing

physical interactiondrugAgenetic associationBC?diseasegenes
Asking forMetforminMetformin?diseasetreatstreatsConstraintsResult:Type 2 diabetes

Query a knowledge graph with SPARQL

SPARQL protocol and RDF query language

RDF: Resource Description Framework (common standard for storing knowledge graphs)

A SPARQL query = a partially completed graph

?’s show what you are looking for

remainder constrains the search

Metformin’s unique id: Q19484
Treats property id: P2175

Metformintreats?disease=

Metformin’s unique id: Q19484
Treats property id: P2175

Metformintreats?disease

Example question: drug repurposing

“For a given drug, what diseases might it be used to treat?”

mode of actionAgonistAntagonistOtherUnknownGENESNPsymbolassociationP-ValueOdds RatioGWAS or PheWASDRUGNameRegistered IndicationNew Indicationrepurposing potentialDISEASEKnown Drug in DrugBankNumber of Medline AbstractsNumber in Clinical Trial RegistryRepurposing Potential
interacts withencoded bygenetic associationtreats???drugprotein?diseasegene

Example question: repurposing Metformin

interacts withencoded bygenetic associationtreats??MetforminSolute carrier family 22member 3prostate cancerSLC22A3

Attachments include information that complements slide content. The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

PubChem

transition text

Identify a unique item

Atorvastatin (CID60823)
identified by InChIKey XUKUURHRXDUEBC-KAYWLYCHSA-N
as defined by molar mass unit (obo:UO_0000055)
expressed as double floating point
also identified in ChEBI (SID103554720)
compound:CID60823
descr:CID60823_Molecular_Weight
obo:UO_0000055
“558.639803”^^xsd:double
sio:CHEMINF_000334
substance:SID103554720
syno:MD5_9a05646d461669f86de312d88ab5748a
ChEBI:39548
“atorvastatin”@en
sio:CHEMINF_000339
sio:has-attribute
sio:is-attribute-of
sio:has-attribute
sio:is-attribute-of
sio:has-unit
rdf:type
rdf:type
rdf:type
sio:has-value
sio:has-value

The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Link an item to similar items

Express similarity:
by molecular formula & bonds
by isotopic composition
by connectivity
by 2 dimension shape
by 3 dimension shape
compound:CID10507504
compound:CID60823
compound:CID23665101
compound:CID10507504
compound:CID10507504
compound:CID10030610
compound:CID11330946
sio:is_stereoisomer_of
sio:has_component

More about linking similar items.

Similarity to other substances
item-1
(3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-yl(314C)pyrrol-1-yl]-3,5-dihydroxyheptanoic acid
XUKUURHRXDUEBC-IEILOPHXSA-N
item-2
(3R,5R)-7-[2-cyclopropyl-5-(4-fluorophenyl)-4-phenyl-3-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxyheptanoic acid
WDKDRVHIGPVFCW-KAYWLYCHSA-N
item-3
(E,3R,5S)-7-[5-[(3-chlorophenyl)carbamoyl]-3,4-bis(4-fluorophenyl)-1-propan-2-ylpyrrol-2-yl]-3,5-dihydroxyhept-6-enoic acid
JNJZDKOQTIGNNB-FDFRSNTISA-N
Has component
Atorvastatin sodium
VVRPOCPLIUDBSA-CNZCJKERSA-M

Define measurement to link similar items

Define items:
similar to Atorvastatin
by chemical structure
by fingerprint
using TanimotoScore
expressed as a double precision decimal
compound:CID60823
sio:CHEMINF_000333
“0.98“^^xsd:double
nbr:CID60823_CID10030610_2DSimilarity
compound:CID10030610
vocab:2D_structural
_similarity
vocab:2D_Fingerprint
_TanimotoScore
nbr:CID60823_CID10030610_2DTanimotoScore
rdf: type
rdf: type
sio:is-output-of
sio:has-measurement-value
sio:has-value

The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Identify a specific dataset from an investigation

A dataset about …
Atorvastatin
recorded for the ChEMBL data source
provided by the EBI organization
about a concept assigned the label:
“Biological Properties”
substance:SID103554720
dcterms:Dataset
skos:Concept
source:ChEMBL
http://www.ebi.ac.uk/chembldb/
source:European_Bioinformatics
_Institute_EBI_ChEMBL
skos:ConceptScheme
vocab:Biological_Properties
vocab:Substance_Categorization
_Classification
“Biological Properties“
sio:has-value
foaf:homepage
dcterms:source
pav:providedBy
rdf:type
rdf:type

The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Identify a specific study & its evidence

Study summarized as: “A new class of anti-inflammatory ester prodrugs”
published by DiscoveryGate
about SID103164874 (CHEBI:15365) and related compound – aspirin
based on a bioassay with the title “Inhibition of ovine COX1 by enzyme immunoassay”
bao:measure-group
reference:PMID19500994
http://www.ncbi.nlm.nih.gov/pubmed/19500994
“Prostaglandin
G/H synthase 1”@en
protein:GI548481
rdf:type
rdf:type
dcterms:title
pr:PR_000006933
“0.35”^^xsd:double
fabio:JournalArticle
“Inhibition of ovine COX1
by enzyme immunoassay”@en
bao:ic50
measuregroup:
AID447528
ops:Micromolar
substance:SID103164874
iao:is-about
endpoint:
SID10316487_AID447528
qudt:unit

The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Provide additional information about a bioassay

Bioassay title: “Primary Cell-based assay for inhibitors of the Retinoic Acid Receptor-related orphan receptor A (RORA)”
summarized as: “probe development efforts to identify novel modulators of ROR” as measured by dose-response cell-based assay for RORA inhibitors
bao:bioassay
bioassay:AID2139
bao:primary-assay
bao:confirmatory-assay
bao:has-assay-stage
bao:has-summary-assay
bao:has-assay-stage
bao:has-assay-stage
bao:summary-assay
measuregroup:AID610
bioassay:AID610
bioassay:AID561
bao:measure-group
rdf:type
rdf:type
bao:has-measure-group
bao:is-measure-group-of

The following uses playful “lorem ipsum” style text to illustrate presentation of additional information.

Abbervail Dream
Blue Diamonds
Bright amazing and wonderful
Dancing around the flames
Everybody knows bird is word
Caramel Sensation
Dairy Cream
Frosty the snowman is a boss
Girls just want to have fun
Got some popsicles in the cellar
Elusive Enchantment
Fat Chance Cinnamon
Insomnia gives me time to
Inspiration slaps me in the face
Last chance for one last dance
Good Luck Charm
Hershey's Kiss
Laugh all day for no reason
Life is a box of chocolates
Live like there is no tomorrow
Ice Cream Mix
Jack Daniels
Make it up as you go
Moms cookies make everything
My room is an organized mess
Kitty Hawk
Last Man Standing
Pluto is still a planet
Six words can mean the world
Sleeping with a giant bear
Made You Look
Nabisco Cracker
Sour candy makes me twitch
The sky is not the limit
There always gonna be another
One in a Million
Peach Blossom
There no place like grandmas
Why whisper what you shout
Your the apple to my pie

Links among PubChem subdomains

At the center: measurments and evidence (bioassays)
Biologics are proteins and genes from specific sources
Items are chemical compounds and substances
Evidence is documented in a study (reference)
similar protein
protein
biosystem
domain
neighbor
gene
measuregroup
endpoint
reference
bioassay
source
substance
synonym
descriptor
inchikey
compound
neighbor
component compound
parent compound
same connectivity
isotopomer
stereoisomer
similar compound

Summary: PubChem Data Model

More about PubChem RDF